The long-term objective is to increase understanding of the regulation of nephron function by exploiting the unique structure of avian kidneys, the highly specialized structure of kidneys of desert rodents, and the specialized transport properties of mammalian and avian nephrons. Avian kidneys have nephrons resembling reptilian nephrons with very simple glomeruli (single capillary loop) that function independently of each, do not contribute directly to the concentrating mechanism, and can cease filtering altogether under some circumstances; nephrons resembling mammalian nephrons that function together in the concentrating mechanism, do not normally cease filtering, but may alter their filtration rates; and both arterial and portal venous blood supplies One strain of chickens has nephrogenic diabetes insipidus. Kidneys of desert rodents have juxtamedullary nephrons several times larger than superficial cortical nephrons and a very long papilla. This structural heterogeneity of nephrons is intermediate between the structural heterogeneity of nephrons in avian kidneys and laboratory rat kidneys. The primary goals involve studies of: 1) glomerular structure and function, including quantitative ultrastructure and filtration will pressures in avian kidneys; and 2) medullary function and concentrating mechanism, including amino acid transport by juxtamedullary mammalian nephrons, the role of amino acids in mammalian medullary function, and concentrating defect(s) in birds with genetic nephrogenic diabetes inipidus. Computer-assisted quantitative ultrastructural analysis of the filtration barrier and the area available for filtration will be used to examine simple avian glomerulus. In vivo micropuncture pressure measurements will help define avian glomerular filtration dynamics in relation to structure in varying diuretic states. In vivo micropuncture and continuous microinfusion, in vitro microperfusion, and amino acid analyses of micropuncture samples and kidney slice extracts will be used to further define amino acid reabsorption distal to the tips of Henle's lops of juxtamedullary nephrons, recycling of amino acids for cellular osmotic and volume regulation during urine concentration in laboratory rats and desert rodents. In vivo clearance determinations and portal infusions and in vitro perfusions of isolated avian collecting ducts and determinations of enzyme activities in these collecting ducts will be used to define the renal defect(s) in chickens with nephrogenic diabetes insipidus.